The experiments described in this proposal are designed to investigate the role of acid-base balance as a limiting factor in muscular work. The plan is to conduct experiments with humans in parallel with those utilizing an in situ dog muscle preparation. The focus in the human experiments is on the role of the respiratory system in responding to the metabolic acidosis of severe exercise--and the possible effects of respiratory muscle fatigue on the compensation for the lactic acidosis. The purpose of the in situ muscle experiments is to investigate the effects of acid-base changes on muscle metabolism and muscle performance without the problems introduced by respiratory changes. In the human experiments, subjects will be tested for changes in work capacity, maximal O2 uptake, and acid-base balance before and after a period of respiratory muscle training and during periods when the work of breathing is altered by substituting helium for N2 as a diluent gas. In the animal experiments, measurements of O2 uptake and CO2 production, muscle lactate release, and muscle and blood acid-base values will be made during periods in which acid-base alterations are induced either by infusion of HC1 or NaHCO3, or by ventilating the animal with different gas mixtures. The long-term objectives of the project are to 1) identify and describe the factors which limit human work capacity in health and in disease states; and 2) to better understand the mechanisms which regulate metabolism during muscular work. These are interesting physiological questions in their own right, but they also are basic to an eventual understanding of the role of exercise as a preventive and therapeutic agent in medicine.